• Detection of early changes in the post-radiosurgery vestibular schwannoma microenvironment using multinuclear MRI

      Lewis, Daniel; email: daniel.lewis-3@postgrad.manchester.ac.uk; McHugh, Damien J.; Li, Ka-loh; Zhu, Xiaoping; Mcbain, Catherine; Lloyd, Simon K.; Jackson, Alan; Pathmanaban, Omar N.; King, Andrew T.; Coope, David J. (Nature Publishing Group UK, 2021-08-03)
      Abstract: Stereotactic radiosurgery (SRS) is an established, effective therapy against vestibular schwannoma (VS). The mechanisms of tumour response are, however, unknown and in this study we sought to evaluate changes in the irradiated VS tumour microenvironment through a multinuclear MRI approach. Five patients with growing sporadic VS underwent a multi-timepoint comprehensive MRI protocol, which included diffusion tensor imaging (DTI), dynamic contrast-enhanced (DCE) MRI and a spiral 23Na-MRI acquisition for total sodium concentration (TSC) quantification. Post-treatment voxelwise changes in TSC, DTI metrics and DCE-MRI derived microvascular biomarkers (Ktrans, ve and vp) were evaluated and compared against pre-treatment values. Changes in tumour TSC and microvascular parameters were observable as early as 2 weeks post-treatment, preceding changes in structural imaging. At 6 months post-treatment there were significant voxelwise increases in tumour TSC (p < 0.001) and mean diffusivity (p < 0.001, repeated-measures ANOVA) with marked decreases in tumour microvascular parameters (p < 0.001, repeated-measures ANOVA). This study presents the first in vivo evaluation of alterations in the VS tumour microenvironment following SRS, demonstrating that changes in tumour sodium homeostasis and microvascular parameters can be imaged as early as 2 weeks following treatment. Future studies should seek to investigate these clinically relevant MRI metrics as early biomarkers of SRS response.
    • The LEGATOS technique: A new tissue‐validated dynamic contrast‐enhanced MRI method for whole‐brain, high‐spatial resolution parametric mapping

      Li, Ka‐Loh; orcid: 0000-0002-6051-9248; email: ka-loh.li-2@manchester.ac.uk; Lewis, Daniel; Coope, David J.; Roncaroli, Federico; Agushi, Erjon; Pathmanaban, Omar N.; King, Andrew T.; Zhao, Sha; Jackson, Alan; Cootes, Timothy; et al. (2021-05-15)
      Purpose: A DCE‐MRI technique that can provide both high spatiotemporal resolution and whole‐brain coverage for quantitative microvascular analysis is highly desirable but currently challenging to achieve. In this study, we sought to develop and validate a novel dual‐temporal resolution (DTR) DCE‐MRI‐based methodology for deriving accurate, whole‐brain high‐spatial resolution microvascular parameters. Methods: Dual injection DTR DCE‐MRI was performed and composite high‐temporal and high‐spatial resolution tissue gadolinium‐based‐contrast agent (GBCA) concentration curves were constructed. The high‐temporal but low‐spatial resolution first‐pass GBCA concentration curves were then reconstructed pixel‐by‐pixel to higher spatial resolution using a process we call LEGATOS. The accuracy of kinetic parameters (Ktrans, vp, and ve) derived using LEGATOS was evaluated through simulations and in vivo studies in 17 patients with vestibular schwannoma (VS) and 13 patients with glioblastoma (GBM). Tissue from 15 tumors (VS) was examined with markers for microvessels (CD31) and cell density (hematoxylin and eosin [H&E]). Results: LEGATOS derived parameter maps offered superior spatial resolution and improved parameter accuracy compared to the use of high‐temporal resolution data alone, provided superior discrimination of plasma volume and vascular leakage effects compared to other high‐spatial resolution approaches, and correlated with tissue markers of vascularity (P ≤ 0.003) and cell density (P ≤ 0.006). Conclusion: The LEGATOS method can be used to generate accurate, high‐spatial resolution microvascular parameter estimates from DCE‐MRI.